Lecture 13 Reactions of Benzenewillson.cm.utexas.edu/Teaching/Chemistry 328N 2019/Files... ·...
Transcript of Lecture 13 Reactions of Benzenewillson.cm.utexas.edu/Teaching/Chemistry 328N 2019/Files... ·...
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Chemistry 328N
Reactions of Benzene
Lecture 13
March 5, 2019
C F 3
C l
NaNH2
NH3(l)
C F 3
NH2
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Chemistry 328N
Electrophilic Aromatic Substitution
E+
E
H
H
+
E
H
H
H
EH
+
+
E+ H+
All EAS reactions
follow this path so we
only need to learn
how to make different
electrophiles, E+
Please be sure
that you can do
this and that it
makes sense to
you!!
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Chemistry 328N
H
H
H H
H + E+
H
E
H
H H
H + H+
H
H H
H
H
H H E
+
The Energetics
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Chemistry 328N
H E
+ E Y + H Yd+ d–
Electrophilic aromatic substitutions include:
Nitration
Sulfonation
Halogenation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
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Chemistry 328N
Relative rates of
Nitration
OH ClH NO2
1000 1.0 0.033 6x10-8
Reactivity
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Chemistry 328N
Real Fast
Pretty fast
Kinda slow
Pretty slow
Slow
Real Slow
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Chemistry 328N
Adding a Second Substiuent
Methoxy is is therefore an “o-p director”
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Chemistry 328N
Adding a Second Substiuent
Nitro is therefore a “meta director”
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Chemistry 328N
Generalization
regioselectivity is controlled by themost activating substituent
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Chemistry 328N
The “Best Man Wins”
Br2
NHCH3
Cl
87%
FeBr3
NHCH3
Cl
Br
strongly
activating
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Chemistry 328N
Reduction of the Nitro Group
HNO3
H2SO4
NO2
Zn
HCl
NH2
Aniline !
The Nitro group is easily reduced. Many reducing
agents can be employed for this transformation
including Sn or Fe in HCl, H2 with Pd/C, etc
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Chemistry 328N
Aniline dyes (Tyrian Purple)
Aniline Dye
Royal Purple Previously
from shell fish secretions
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Chemistry 328N
Diazonium Salts
Diazonium Salt
Acts like
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Chemistry 328N
Mechanism of Diazonium Salt formation
H O N O + H+
H 2O
+
nitrosoniumion
R NH 2
N O++
R N
H
H
N O+
N-nitrosoammoniumion
R N
H
H
N O+
+ H 2O R N
H
N O + H 3O+
N-nitrosamine
R N
H
N Otautomerization
R N N OH
a diazenol
R N N OH + H+ R N N O
H
H
R N N OH
HR N N + H 2O
+
a diazoniumion
N OOH
H
+
N OOH
H
+
+
+
N O+
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Chemistry 328N
Reactions of Diazonium Salts
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Chemistry 328N
Diazonium Salts
⚫ The -N2+ group of an arenediazonium salt can be
replaced in a regioselective manner by these groups
Schiemann
reaction
Sandmeyer
reactionAr-N 2
+ (-N2
)
Ar-Cl
Ar-Br
Ar-I
Ar-F
KCN, CuCN
Ar-H
HCl, CuCl
Ar-CN
HBr, CuBr
KI
H3
PO2
HBF4
Ar-OHH
2O
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Chemistry 328N
Practice
NH2
CH3
ClCH3
CCH3
N CH2 NH2
CH3
NH2
CH3
ClCl
CH3
ClCl
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Chemistry 328N
Practice…work backwardsOh No….two o,p directors meta to one another???
C l
B r
?????
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Chemistry 328N
Synthesis Strategy
? ?
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Chemistry 328N
Substitution Reactions
⚫ Aryl halides do not undergo nucleophilic
substitution by either SN1 or SN2 pathways!
But…..
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Chemistry 328N
But….this is fact⚫ When heated under pressure with aqueous NaOH,
chlorobenzene is converted to sodium phenoxide
– neutralization with HCl gives phenol????? What is this??
Sodium phenoxide
Chloro-benzene
++pressure, 300oC
+
Cl O-Na
+
2 NaOHH2 O
NaCl H2 O
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Chemistry 328N
Also fact….
⚫ The same reaction with 2-chlorotoluene gives a
mixture of ortho- and meta-cresol???? Ortho and
meta….huh????
3-Methylphenol (m-Cresol)
2-Methylphenol (o-Cresol)
+
CH3Cl OH
CH3 CH3
OH
1 . NaOH , heat, pressure
2. HCl, H2O
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Chemistry 328N
Also true
⚫ The same type of reaction can be brought about by
the use of sodium amide in liquid ammonia
++(-33oC)
+
Cl
CH 3 CH 3
NH 2
NH 2
CH 3
NaNH 2
NH 3 (l)NaCl
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Chemistry 328N
Proposed Benzyne Intermediate
⚫ -elimination of HX gives a “benzyne”
intermediate, that then adds the nucleophile to
give products
A benzyne intermediate
CH3
H
CH3
Cl
NaNH 2
-elimin-ation
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Chemistry 328N
CH3
Cl
HNH2
-
CH3
NH2-
CH3
NH2- NH2
CH3
H NH2
NH2
CH3
H
NH2-+
CH3
NH2
H NH2
CH3
NH2
H
+ NH2-
Proposed Benzyne Intermediate
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Chemistry 328N
Proposed Benzyne Intermediate
Another Mystery??
CF3
Cl
NaNH2
NH3(l)
CF3
NH2
More than 95% of the product
is the meta isomer??
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Chemistry 328N
Nucleophilic Addition-Elimination
⚫ When an aryl halide contains strongly electron-
withdrawing -NO2 groups ortho and/or para to X,
nucleophilic aromatic sub. takes place readily
100 oC
Sodium 2,4-dinitro phenoxide1-Chloro-2,4- dinitrobenzene
NO2
Cl
NO2 NO2
O-
Na+
NO2Na 2 CO3 , H 2 O
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Chemistry 328N
Meisenheimer Complex
fast
slow, rate-limiting+
••
•••• ••
••
••
+
••
••
•••••• ••
+
-
+
••
••
••••••
+
A Meisenheimer complex
-
-
N Cl
NO2
O
O
N
O
O
NO2
NuCl
NuN
O
ONO2
Nu-
Cl-
(1)
(2)
-
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Chemistry 328N
Addition Elimination
F
NO2
CH3O-
CH3OH
NO2
OCH3